par Levet, Vincent ;Amighi, Karim ;Wauthoz, Nathalie
Référence Journée des Doctorants de sciences biomédicales, dentaires, sciences médicales et pharmaceutiques (15th: 17/12/2015: Erasme, Belgique)
Publication Non publié, 2015-12-17
Poster de conférence
Résumé : Background: Cisplatin for lung cancer therapy is currently administered through a systemic I.V. infusion. Despite its great potency against tumors, cisplatin exerts very high and dose-limiting acute and chronic nephrotoxicity, ototoxicity and myelosuppression. We previously showed that a local administration helps increasing the concentration of cisplatin inside the lungs while significantly decreasing the systemic exposition. In order to safely deliver cisplatin to the lungs, we developed immediate and controlled-release Dry Powders for Inhalation (DPI) for human use.Methods: Cisplatin microcrystals were obtained by reducing bulk cisplatin in suspension with high shear mixing and high pressure homogenizing using an Avestin Emulsiflex C5. The obtained microsuspension was then spray-dried with a Büchi Mini Spray-Dryer, either directly or after the addition of solubilized lipidic excipients to obtain a hydrophobic coating of microcrystals. Microsuspensions and DPIs were then characterized by particle size distribution (PSD) by laser diffraction using a Malvern Mastersizer 3000© Hydro MV. Aerodynamic properties of DPIs were assessed with a Copley Fast Screening Impactor© at 100 L/min during 2.4s. Dissolution tests were realized on the respirable fraction of DPIs in modified simulated lung fluid. Particle shape was established by SEM analysis.Results: Produced DPIs showed small and narrow PSD and very high respirable fractions (from 34 to 52% Fine Particle Fraction of the nominal dose, i.e. dae of particles ≤ 5 um) for both immediate and controlled-release formulations. While uncoated formulations of cisplatin were totally dissolved in less than 15 minutes, lipid-coated formulations showed a 24h controlled-release of cisplatin in lung media, with a very high cisplatin content (up to 75% w/w) and a limited burst-effect (less than 50% in 4 hours).Conclusion: We showed that reproducible and up-scalable methods can be used to produce immediate and controlled-release cisplatin-based DPIs for human use with good aerodynamic and dissolution properties.